PT792167E - Conjugados monofuncionais e/ou polifuncionais da polilisina - Google Patents
Conjugados monofuncionais e/ou polifuncionais da polilisina Download PDFInfo
- Publication number
- PT792167E PT792167E PT95940329T PT95940329T PT792167E PT 792167 E PT792167 E PT 792167E PT 95940329 T PT95940329 T PT 95940329T PT 95940329 T PT95940329 T PT 95940329T PT 792167 E PT792167 E PT 792167E
- Authority
- PT
- Portugal
- Prior art keywords
- ole
- farcys
- nac
- myr
- pal
- Prior art date
Links
- 229920000656 polylysine Polymers 0.000 claims abstract description 66
- 108010039918 Polylysine Proteins 0.000 claims abstract description 64
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 27
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 9
- 230000001363 autoimmune Effects 0.000 claims abstract description 6
- 208000015181 infectious disease Diseases 0.000 claims abstract description 6
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 6
- 208000026350 Inborn Genetic disease Diseases 0.000 claims abstract description 5
- 208000016361 genetic disease Diseases 0.000 claims abstract description 5
- 230000002458 infectious effect Effects 0.000 claims abstract description 5
- 230000002062 proliferating effect Effects 0.000 claims abstract description 5
- 230000000472 traumatic effect Effects 0.000 claims abstract description 5
- 206010067722 Toxic neuropathy Diseases 0.000 claims abstract description 4
- 231100000126 Toxic neuropathy Toxicity 0.000 claims abstract description 4
- 238000011282 treatment Methods 0.000 claims description 36
- 238000002360 preparation method Methods 0.000 claims description 33
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 24
- 235000018417 cysteine Nutrition 0.000 claims description 24
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Natural products C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 20
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 19
- 229930195729 fatty acid Natural products 0.000 claims description 19
- 239000000194 fatty acid Substances 0.000 claims description 19
- 150000004665 fatty acids Chemical class 0.000 claims description 19
- 208000035475 disorder Diseases 0.000 claims description 18
- -1 imidazol-5-ylmethyl group Chemical group 0.000 claims description 18
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 17
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 208000034189 Sclerosis Diseases 0.000 claims description 14
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 13
- BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 claims description 13
- 235000001014 amino acid Nutrition 0.000 claims description 12
- 235000012000 cholesterol Nutrition 0.000 claims description 12
- 150000001413 amino acids Chemical class 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 10
- 238000012856 packing Methods 0.000 claims description 10
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 229940088597 hormone Drugs 0.000 claims description 9
- 239000005556 hormone Substances 0.000 claims description 9
- 230000002209 hydrophobic effect Effects 0.000 claims description 9
- 206010036030 Polyarthritis Diseases 0.000 claims description 8
- 229930003427 Vitamin E Natural products 0.000 claims description 8
- 206010003246 arthritis Diseases 0.000 claims description 8
- 230000001588 bifunctional effect Effects 0.000 claims description 8
- 150000004985 diamines Chemical class 0.000 claims description 8
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 201000001119 neuropathy Diseases 0.000 claims description 8
- 230000007823 neuropathy Effects 0.000 claims description 8
- 208000030428 polyarticular arthritis Diseases 0.000 claims description 8
- 235000019165 vitamin E Nutrition 0.000 claims description 8
- 239000011709 vitamin E Substances 0.000 claims description 8
- 229940046009 vitamin E Drugs 0.000 claims description 8
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 7
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 7
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims description 7
- 229930003268 Vitamin C Natural products 0.000 claims description 7
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 7
- 239000011719 vitamin A Substances 0.000 claims description 7
- 235000019155 vitamin A Nutrition 0.000 claims description 7
- 235000019154 vitamin C Nutrition 0.000 claims description 7
- 239000011718 vitamin C Substances 0.000 claims description 7
- 229940045997 vitamin a Drugs 0.000 claims description 7
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 6
- 208000016604 Lyme disease Diseases 0.000 claims description 6
- 208000019695 Migraine disease Diseases 0.000 claims description 6
- 235000021314 Palmitic acid Nutrition 0.000 claims description 6
- 229960004373 acetylcholine Drugs 0.000 claims description 6
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 6
- 230000003412 degenerative effect Effects 0.000 claims description 6
- 206010015037 epilepsy Diseases 0.000 claims description 6
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 claims description 5
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 5
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 5
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 208000031886 HIV Infections Diseases 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- 239000005642 Oleic acid Substances 0.000 claims description 5
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 5
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 claims description 5
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 5
- 150000003505 terpenes Chemical class 0.000 claims description 5
- 208000030507 AIDS Diseases 0.000 claims description 4
- 206010012289 Dementia Diseases 0.000 claims description 4
- 208000037357 HIV infectious disease Diseases 0.000 claims description 4
- 235000021355 Stearic acid Nutrition 0.000 claims description 4
- 230000006378 damage Effects 0.000 claims description 4
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 4
- 206010027599 migraine Diseases 0.000 claims description 4
- 210000005036 nerve Anatomy 0.000 claims description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 4
- 239000008117 stearic acid Substances 0.000 claims description 4
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 claims description 4
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 235000021313 oleic acid Nutrition 0.000 claims description 3
- 238000004806 packaging method and process Methods 0.000 claims description 3
- 208000014644 Brain disease Diseases 0.000 claims description 2
- 206010048962 Brain oedema Diseases 0.000 claims description 2
- 206010019196 Head injury Diseases 0.000 claims description 2
- 208000026139 Memory disease Diseases 0.000 claims description 2
- 208000008348 Post-Concussion Syndrome Diseases 0.000 claims description 2
- 206010039966 Senile dementia Diseases 0.000 claims description 2
- 208000010112 Spinocerebellar Degenerations Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 201000004810 Vascular dementia Diseases 0.000 claims description 2
- 208000006752 brain edema Diseases 0.000 claims description 2
- 201000001981 dermatomyositis Diseases 0.000 claims description 2
- 235000015872 dietary supplement Nutrition 0.000 claims description 2
- 208000005987 polymyositis Diseases 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 230000001953 sensory effect Effects 0.000 claims description 2
- 230000002739 subcortical effect Effects 0.000 claims description 2
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 claims description 2
- 230000002889 sympathetic effect Effects 0.000 claims description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 2
- 235000019195 vitamin supplement Nutrition 0.000 claims description 2
- 208000007465 Giant cell arteritis Diseases 0.000 claims 1
- 239000004642 Polyimide Substances 0.000 claims 1
- 208000010641 Tooth disease Diseases 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 229920001721 polyimide Polymers 0.000 claims 1
- 229920001228 polyisocyanate Polymers 0.000 claims 1
- 239000005056 polyisocyanate Substances 0.000 claims 1
- 206010043207 temporal arteritis Diseases 0.000 claims 1
- 206010043778 thyroiditis Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 12
- 201000010099 disease Diseases 0.000 abstract description 9
- 239000000243 solution Substances 0.000 description 85
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 238000009739 binding Methods 0.000 description 13
- 239000002253 acid Substances 0.000 description 11
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 11
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 10
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 10
- 238000000502 dialysis Methods 0.000 description 10
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- JTEJPPKMYBDEMY-UHFFFAOYSA-N 5-methoxytryptamine Chemical compound COC1=CC=C2NC=C(CCN)C2=C1 JTEJPPKMYBDEMY-UHFFFAOYSA-N 0.000 description 8
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 7
- 150000008065 acid anhydrides Chemical class 0.000 description 7
- 150000001412 amines Chemical group 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 230000001684 chronic effect Effects 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 238000010254 subcutaneous injection Methods 0.000 description 7
- 239000007929 subcutaneous injection Substances 0.000 description 7
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 6
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 6
- 150000001718 carbodiimides Chemical class 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 229930002330 retinoic acid Natural products 0.000 description 6
- 229960001727 tretinoin Drugs 0.000 description 6
- GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 5
- 229940087168 alpha tocopherol Drugs 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical compound O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 5
- 239000000186 progesterone Substances 0.000 description 5
- 229960003387 progesterone Drugs 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 229940014800 succinic anhydride Drugs 0.000 description 5
- 229960003080 taurine Drugs 0.000 description 5
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 5
- 229960000984 tocofersolan Drugs 0.000 description 5
- 235000004835 α-tocopherol Nutrition 0.000 description 5
- 239000002076 α-tocopherol Substances 0.000 description 5
- 229940097276 5-methoxytryptamine Drugs 0.000 description 4
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 229930182817 methionine Natural products 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- SNKZJIOFVMKAOJ-UHFFFAOYSA-N 3-Aminopropanesulfonate Chemical compound NCCCS(O)(=O)=O SNKZJIOFVMKAOJ-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 239000005057 Hexamethylene diisocyanate Substances 0.000 description 3
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 3
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 239000008351 acetate buffer Substances 0.000 description 3
- 238000004873 anchoring Methods 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000003943 catecholamines Chemical class 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- 239000000385 dialysis solution Substances 0.000 description 3
- 229960003638 dopamine Drugs 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- RRAMGCGOFNQTLD-UHFFFAOYSA-N hexamethylene diisocyanate Chemical compound O=C=NCCCCCCN=C=O RRAMGCGOFNQTLD-UHFFFAOYSA-N 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 238000005063 solubilization Methods 0.000 description 3
- 230000007928 solubilization Effects 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- KJTLQQUUPVSXIM-ZCFIWIBFSA-M (R)-mevalonate Chemical compound OCC[C@](O)(C)CC([O-])=O KJTLQQUUPVSXIM-ZCFIWIBFSA-M 0.000 description 2
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- SYSLNQMKLROGCL-BCYUYYMPSA-N S-[(2E,6E)-farnesyl]-L-cysteine zwitterion Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CSC[C@H](N)C(O)=O SYSLNQMKLROGCL-BCYUYYMPSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 229940009098 aspartate Drugs 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- VHRGRCVQAFMJIZ-UHFFFAOYSA-N cadaverine Chemical compound NCCCCCN VHRGRCVQAFMJIZ-UHFFFAOYSA-N 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 125000005442 diisocyanate group Chemical group 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid ester group Chemical group C(CCCCCCCCCCC)(=O)O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 210000005064 dopaminergic neuron Anatomy 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- VVIUBCNYACGLLV-UHFFFAOYSA-N hypotaurine Chemical compound [NH3+]CCS([O-])=O VVIUBCNYACGLLV-UHFFFAOYSA-N 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 210000004558 lewy body Anatomy 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 210000002161 motor neuron Anatomy 0.000 description 2
- 231100000189 neurotoxic Toxicity 0.000 description 2
- 230000002887 neurotoxic effect Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
- 239000000700 radioactive tracer Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 2
- 125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 2
- 150000003455 sulfinic acids Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- DZCBKUAAGVVLOX-UHFFFAOYSA-N 1-morpholin-4-ylethanol Chemical compound CC(O)N1CCOCC1 DZCBKUAAGVVLOX-UHFFFAOYSA-N 0.000 description 1
- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 description 1
- XRXTWSABNBANQL-UHFFFAOYSA-N 2-amino-3-[bis(2-chloropropyl)carbamoyloxy]propanoic acid Chemical compound CC(Cl)CN(CC(C)Cl)C(=O)OCC(N)C(O)=O XRXTWSABNBANQL-UHFFFAOYSA-N 0.000 description 1
- KZMAWJRXKGLWGS-UHFFFAOYSA-N 2-chloro-n-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-n-(3-methoxypropyl)acetamide Chemical compound S1C(N(C(=O)CCl)CCCOC)=NC(C=2C=CC(OC)=CC=2)=C1 KZMAWJRXKGLWGS-UHFFFAOYSA-N 0.000 description 1
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical group C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 1
- 229940000681 5-hydroxytryptophan Drugs 0.000 description 1
- KVNPSKDDJARYKK-JTQLQIEISA-N 5-methoxytryptophan Chemical compound COC1=CC=C2NC=C(C[C@H](N)C(O)=O)C2=C1 KVNPSKDDJARYKK-JTQLQIEISA-N 0.000 description 1
- KHOITXIGCFIULA-UHFFFAOYSA-N Alophen Chemical compound C1=CC(OC(=O)C)=CC=C1C(C=1N=CC=CC=1)C1=CC=C(OC(C)=O)C=C1 KHOITXIGCFIULA-UHFFFAOYSA-N 0.000 description 1
- 206010002027 Amyotrophy Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 241000589968 Borrelia Species 0.000 description 1
- 101100284398 Bos taurus BoLA-DQB gene Proteins 0.000 description 1
- 208000002381 Brain Hypoxia Diseases 0.000 description 1
- RFDVZWOFSNTAJH-UHFFFAOYSA-N CC(C(=O)N)=C.[Na] Chemical compound CC(C(=O)N)=C.[Na] RFDVZWOFSNTAJH-UHFFFAOYSA-N 0.000 description 1
- 101100074846 Caenorhabditis elegans lin-2 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010008025 Cerebellar ataxia Diseases 0.000 description 1
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010063907 Glutathione Reductase Proteins 0.000 description 1
- 102100036442 Glutathione reductase, mitochondrial Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000007987 MES buffer Substances 0.000 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 101100497386 Mus musculus Cask gene Proteins 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- 235000021360 Myristic acid Nutrition 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 235000021319 Palmitoleic acid Nutrition 0.000 description 1
- 239000005700 Putrescine Substances 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000036626 alertness Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940124277 aminobutyric acid Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 229940033495 antimalarials Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000000768 catecholaminergic effect Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 208000006111 contracture Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002594 corticospinal effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000002089 crippling effect Effects 0.000 description 1
- 150000001944 cysteine derivatives Chemical class 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- HAPOVYFOVVWLRS-UHFFFAOYSA-N ethosuximide Chemical compound CCC1(C)CC(=O)NC1=O HAPOVYFOVVWLRS-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 150000002433 hydrophilic molecules Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003601 intercostal effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 229960004232 linoleic acid Drugs 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 230000001730 monoaminergic effect Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 210000001009 nucleus accumben Anatomy 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- LDCYZAJDBXYCGN-UHFFFAOYSA-N oxitriptan Natural products C1=C(O)C=C2C(CC(N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229960001639 penicillamine Drugs 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940063673 spermidine Drugs 0.000 description 1
- 229940063675 spermine Drugs 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical group OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000000982 vasogenic effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940063682 zarontin Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicinal Preparation (AREA)
- Polyamides (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9413861A FR2727117A1 (fr) | 1994-11-18 | 1994-11-18 | Utilisation de conjugues de la polylysine pour la preparation de medicaments utiles dans le traitement des maladies neurodegeneratives et des affections degeneratives a caractere autoimmun |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT792167E true PT792167E (pt) | 2001-12-28 |
Family
ID=9468953
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT95940329T PT792167E (pt) | 1994-11-18 | 1995-11-17 | Conjugados monofuncionais e/ou polifuncionais da polilisina |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US6114388A (https=) |
| EP (1) | EP0792167B1 (https=) |
| JP (1) | JP4128618B2 (https=) |
| AT (1) | ATE202487T1 (https=) |
| AU (1) | AU694825B2 (https=) |
| CA (1) | CA2205557C (https=) |
| DE (1) | DE69521521T2 (https=) |
| DK (1) | DK0792167T3 (https=) |
| ES (1) | ES2161915T3 (https=) |
| FR (1) | FR2727117A1 (https=) |
| GR (1) | GR3036710T3 (https=) |
| NZ (1) | NZ297040A (https=) |
| PT (1) | PT792167E (https=) |
| WO (1) | WO1996015810A1 (https=) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AUPO104396A0 (en) * | 1996-07-17 | 1996-08-08 | Biomolecular Research Institute Limited | Antiviral linear polymers |
| CA2284729A1 (en) | 1997-04-18 | 1998-10-29 | Novartis Ag | Neoglycoproteins |
| FR2763853B1 (fr) * | 1997-05-28 | 2000-01-07 | Oreal | Association d'un retinoide avec un polymere polyamine |
| DE19732139C2 (de) | 1997-07-25 | 2002-10-10 | Max Planck Gesellschaft | Mesomorphe Komplexe aus Vitamin A-Säure und kationischen Polyelektrolyten, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen |
| FR2773808B1 (fr) * | 1998-01-20 | 2000-05-05 | Sagebo | Composes susceptibles de pieger les ions metalliques, leur procede d'obtention et leur utilisation |
| US6919076B1 (en) * | 1998-01-20 | 2005-07-19 | Pericor Science, Inc. | Conjugates of agents and transglutaminase substrate linking molecules |
| US6686446B2 (en) * | 1998-03-19 | 2004-02-03 | The Regents Of The University Of California | Methods and compositions for controlled polypeptide synthesis |
| GB9811059D0 (en) * | 1998-05-23 | 1998-07-22 | Univ Strathclyde | Polyamino acid vesicles |
| ES2235499T3 (es) | 1998-07-30 | 2005-07-01 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Uso de derivados de propionil l-carnitina y de acetil l-carnitina en la preparacion de medicamentos con actividad anticancerigena. |
| CA2372526A1 (en) * | 1999-05-10 | 2000-11-16 | Michael D. Wyrsta | Methods and compositions for controlled polypeptide synthesis |
| US20020072509A1 (en) * | 2000-10-11 | 2002-06-13 | Stein Donald Gerald | Methods for the treatment of a traumatic central nervous system injury |
| US7658926B2 (en) * | 2001-09-14 | 2010-02-09 | Opexa Pharmaceuticals, Inc. | Autologous T-cell vaccines materials and methods |
| FR2842422B1 (fr) * | 2002-07-16 | 2006-06-30 | Univ Aix Marseille Ii | Compositions destinees au traitement des neuropathies peripheriques, preparation et utilisations |
| RU2327487C2 (ru) * | 2002-08-08 | 2008-06-27 | Бейлор Колледж Оф Медисин | Выделение и идентификация т-клеток |
| DE60321363D1 (de) * | 2002-08-28 | 2008-07-10 | Millipore Corp | Verfahren zur aufreinigung von sequenzierungsreaktionen |
| US8338648B2 (en) * | 2004-06-12 | 2012-12-25 | Signum Biosciences, Inc. | Topical compositions and methods for epithelial-related conditions |
| US7473687B2 (en) * | 2005-03-24 | 2009-01-06 | Emory University | Methods for the treatment of a traumatic central nervous system injury |
| US20090325920A1 (en) | 2005-03-24 | 2009-12-31 | Emory University | Methods for the treatment of a traumatic central nervous system injury |
| FR2886153B1 (fr) * | 2005-05-27 | 2009-04-10 | Gemac Sa | Composition destinee au traitement de la sclerose en plaques |
| CA2651328A1 (en) * | 2006-05-05 | 2007-11-15 | Opexa Therapeutics | T-cell vaccine |
| FR2905868B1 (fr) * | 2006-09-18 | 2012-12-21 | Gemac | Composition destinee au traitement de la sclerose laterale amyotrophique |
| CN101622017B (zh) | 2006-12-22 | 2018-09-11 | 克罗马制药有限责任公司 | 聚合物的用途 |
| FR2913335B1 (fr) | 2007-03-06 | 2009-06-05 | Michel Geffard | Utilisation de conjugues d'acides gras et de poly-l-lysine pour lutter contre des microorganismes pathogenes. |
| EP2085082A1 (en) * | 2008-01-29 | 2009-08-05 | Nutromnia S.R.L. | Treatment of cognitive decline |
| EP2696868A1 (en) * | 2011-04-12 | 2014-02-19 | Nestec S.A. | Nutritional compositions including branched chain fatty acids and methods of using same |
| SI3116887T1 (sl) | 2014-03-13 | 2021-06-30 | Universitaet Basel | Ogljikohidratni ligandi, ki se vežejo na protitelesa img proti glikoproteinu, ki je povezan z mielinom |
| FR3030524B1 (fr) * | 2014-12-17 | 2017-01-20 | Hydro-Fill | Utilisation de pll pour ameliorer la stabilite de molecules en solution |
| US11091591B2 (en) | 2015-09-16 | 2021-08-17 | Universität Basel | Carbohydrate ligands that bind to antibodies against glycoepitopes of glycosphingolipids |
| FR3048616B1 (fr) * | 2016-03-14 | 2018-04-06 | Polyneuros | Polycomplexes de composes poly-lysine pour la prevention et/ou la lutte contre la sclerose laterale amyotrophique |
| FR3122573B1 (fr) * | 2021-05-10 | 2024-03-29 | Hydro Fill Tech | Compositions de conjugués poly-lysine et de micelles et/ou de copolymères de poly-lysine |
| FR3122571B1 (fr) * | 2021-05-10 | 2023-05-12 | Hydro Fill Tech | Compositions et leur utilisation pour rétablir la perméabilité intestinale et/ou prévenir ou lutter contre des maladies multifactorielles |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55500053A (https=) * | 1978-01-16 | 1980-01-31 | ||
| DE3546150A1 (de) * | 1985-06-24 | 1987-01-22 | Hoechst Ag | Membrananker-wirkstoffkonjugat, seine herstellung sowie seine verwendung |
| GB9004538D0 (en) * | 1990-02-28 | 1990-04-25 | Offord Robin E | Chemical compounds |
| DK0575545T3 (da) * | 1991-03-15 | 2003-09-15 | Amgen Inc | Pegylering af polypeptider |
| WO1993025197A1 (en) * | 1992-06-12 | 1993-12-23 | Affymax Technologies N.V. | Compositions and methods for enhanced drug delivery |
| FR2705234B1 (fr) * | 1993-05-19 | 1995-08-04 | Geffard Michel | Utilisation de molécules reconnues par des autoanticorps de sérums humains pour le diagnostic ou le traitement du SIDA. |
-
1994
- 1994-11-18 FR FR9413861A patent/FR2727117A1/fr active Granted
-
1995
- 1995-11-17 AT AT95940329T patent/ATE202487T1/de not_active IP Right Cessation
- 1995-11-17 DE DE69521521T patent/DE69521521T2/de not_active Expired - Lifetime
- 1995-11-17 PT PT95940329T patent/PT792167E/pt unknown
- 1995-11-17 AU AU41811/96A patent/AU694825B2/en not_active Ceased
- 1995-11-17 JP JP51662296A patent/JP4128618B2/ja not_active Expired - Fee Related
- 1995-11-17 CA CA002205557A patent/CA2205557C/en not_active Expired - Lifetime
- 1995-11-17 WO PCT/FR1995/001517 patent/WO1996015810A1/fr not_active Ceased
- 1995-11-17 DK DK95940329T patent/DK0792167T3/da active
- 1995-11-17 ES ES95940329T patent/ES2161915T3/es not_active Expired - Lifetime
- 1995-11-17 US US08/836,199 patent/US6114388A/en not_active Expired - Lifetime
- 1995-11-17 EP EP95940329A patent/EP0792167B1/fr not_active Expired - Lifetime
- 1995-11-17 NZ NZ297040A patent/NZ297040A/xx unknown
-
2001
- 2001-09-26 GR GR20010401567T patent/GR3036710T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2205557C (en) | 2008-07-15 |
| EP0792167B1 (fr) | 2001-06-27 |
| FR2727117B1 (https=) | 1997-02-21 |
| NZ297040A (en) | 1999-05-28 |
| DK0792167T3 (da) | 2001-10-29 |
| WO1996015810A1 (fr) | 1996-05-30 |
| AU4181196A (en) | 1996-06-17 |
| US6114388A (en) | 2000-09-05 |
| AU694825B2 (en) | 1998-07-30 |
| FR2727117A1 (fr) | 1996-05-24 |
| DE69521521T2 (de) | 2002-04-25 |
| JPH10511643A (ja) | 1998-11-10 |
| ATE202487T1 (de) | 2001-07-15 |
| CA2205557A1 (en) | 1996-05-30 |
| JP4128618B2 (ja) | 2008-07-30 |
| ES2161915T3 (es) | 2001-12-16 |
| DE69521521D1 (de) | 2001-08-02 |
| EP0792167A1 (fr) | 1997-09-03 |
| GR3036710T3 (en) | 2001-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PT792167E (pt) | Conjugados monofuncionais e/ou polifuncionais da polilisina | |
| Holdiness | Clinical pharmacokinetics of N-acetylcysteine | |
| ES2380622T5 (es) | Compuestos de anfetamina resistentes al abuso | |
| ES2472545T3 (es) | Profármacos de diclofenaco solubles en agua con carga positiva y con una tasa de penetración en piel muy rápida | |
| PT1073432E (pt) | Utilização da d-alanina ou da d-serina para o tratamento da esquizofrenia | |
| JP2002522357A5 (https=) | ||
| JP2002522357A (ja) | 胆汁酸を有する清浄水溶液型製剤の調剤 | |
| EA025735B1 (ru) | Способ лечения портальной гипертензии с использованием l-орнитина в сочетании по меньшей мере с одним из соединений, выбранных из фенилацетата и фенилбутирата | |
| CN106659711A (zh) | 呈现长期稳定性的褪黑素注射剂的持久制剂 | |
| CN115701985A (zh) | 具有硫胺素的二氢槲皮素制剂 | |
| FR2775901A1 (fr) | Sels de cetoacides et de derives amines, et leur utilisation pour la preparation de medicaments | |
| CN108366983A (zh) | L-鸟氨酸苯乙酸盐制剂 | |
| EP1372617B1 (fr) | Sels de cetoacides et d'acides amines gastroresistants et leur utilisation pour la preparation de medicaments | |
| US20100286080A1 (en) | Aqueous composition comprising chitosan and an acidic drug | |
| Santos et al. | Involvement of nuclear factor κB and descending pain pathways in the anti-hyperalgesic effect of β-citronellol, a food ingredient, complexed in β-cyclodextrin in a model of complex regional pain syndrome-Type 1 | |
| AU713902B2 (en) | Diclofenac/gamma-cyclodextrin inclusion compounds | |
| EP0305968A2 (en) | Compositions against protozoal diseases | |
| AU2005285040A1 (en) | D-methionine formulation with improved biopharmaceutical properties | |
| AU2005270573B2 (en) | Novel formulation for L-tryptophane comprising carbidopa/benserazide | |
| BRPI0714012A2 (pt) | formulaÇço farmacÊutica aquosa de Ácido 4-[((4-carboxibutil)-{2-[(4-fenetil-benzil)àxi]-fenetil}am ino)metil]benzàico | |
| CN118697690A (zh) | 一种巴氯芬鼻脑递释组合物 | |
| US20100130612A1 (en) | Composition containing chitosan for sustained drug release | |
| US5804218A (en) | Methods and compositions for inhibiting enterohepatic cycling of bilirubin | |
| WO2024149252A1 (zh) | 磷酸镁物质、包含其的药物组合物及其用途 | |
| PT88309B (pt) | Processo para a preparacao de esteres de butilo terciario de drogas anticancerigenas e sua utilizacao para melhorar a administracao das drogas ao cerebro |